Hypertension is a complex multifactorial and polygenic disorder that is thought to result from an interaction between an individual's genetic background and various environmental factors (see non-patent document 1). Given that hypertension is a major risk factor for coronary artery disease, stroke, and chronic renal failure, prevention of hypertension is an important public health goal. One approach to preventing the development of hypertension is to identify susceptibility genes. Linkage studies (see non-patent documents 2 to 4) and association studies with candictae genes (see non-patent documents 5 to 8) have implicated various chromosomal loci and genes in predisposition to hypertension. Although genetic epidemiological studies have suggested that certain genetic variants, including polymorphisms in the genes encoding angiotensinogen (non-patent document 5), α-adducin (non-patent document 6), the β3 subunit of G proteins (non-patent document 7) and the β2-adrenergic receptor (non-patent document 8), etc. increase the risk for hypertension, the genes that contribute to genetic susceptibility to hypertension remain to be identified definitively. In addition, because of ethnic divergence of gene polymorphisms, it is important to construct a database of polymorphisms related to hypertension in each ethnic group.
Non-patent document 1: Lifton R P, Gharavi A G, Geller D S. Molecular mechanisms of human hypertension. Cell. 2001; 104: 545-556.
Non-patent document 2: Xu X, Rogus J J, Terwedow H A, Yang J, Wang Z, Chen C, Niu T, Wang B, Xu H, Weiss S, Schork N J, Fang Z. An extreme-sib-pair genome scan for genes regulating blood pressure. Am J Hum Genet. 1999; 64: 1694-1701.
Non-patent document 3: Krushkal J, Ferrell R, Mockrin S C, Turner S T, Sing C F, Boerwinkle E. Genome-wide linkage analysis of systolic blood pressure using highly discordant siblings. Circulation. 1999; 99: 1407-141.
Non-patent document 4: Rice T, Rankinen T, Province M A, Chagnon Y C, Pérusse L, Borecki I B, Bouchard C, Rao D C. Genome-wide linkage analysis of systolic and diastolic blood pressure: the Québec Family Study. Circulation. 2000; 102: 1956-1963.
Non-patent document 5: Jeunemaitre X, Soubrier F, Kotelevtsev Y V, Lifton R P, Williams C S, Charru A, Hunt S C, Hopkins P N, Williams R R, Laouel J-M, Corvol P. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992; 71: 169-180.
Non-patent document 6: Cusi D, Barlassina C, Azzani T, Casari O, Citterio L, Devoto M, Gloriso N, Lanzani C, Manunta P, Righetti M, Rivera R, Stella P, Troffa C, Zagato L, Bianchi G. Polymorphisms of a-adducin and salt sensitivity in patients with essential hypertension. Lancet. 1997; 349: 1353-1357.
Non-patent document 7: Siffert W, Rosskop D, Siffert G, Busch S, Moritz A, Erbel R, Sharma A M, Ritz E, Wichmann H-E, Jakobs K H, Horsthemke B. Association of a human G-protein β3 subunit variant with hypertension. Nat Genet. 1998; 18: 45-48.
Non-patent document 8: Bray M S, Krushkal J, Li L, Ferrell R, Kardia S, Sing C F, Turner S T, Boerwinkle E. Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for hypertension. Circulation. 2000; 101: 2877-2882.